Fork coupling directs DNA replication elongation and termination.

DNA replication is initiated at multiple loci to ensure timely duplication of eukaryotic genomes. Sister replication forks progress bidirectionally, and replication terminates when two convergent forks encounter one another. To investigate the coordination of replication forks, we developed a replication-associated in situ HiC method to capture chromatin interactions involving nascent DNA. We identify more than 2000 fountain-like structures of chromatin contacts in human and mouse genomes, indicative of coupling of DNA replication forks. Replication fork interaction not only occurs between sister forks but also involves forks from two distinct origins to predetermine replication termination. Termination-associated chromatin fountains are sensitive to replication stress and lead to coupled forks-associated genomic deletions in cancers. These findings reveal the spatial organization of DNA replication forks within the chromatin context.

Bacterial diversity of herbal rhizospheric soils in Ordos desert steppes under different degradation gradients.

Objectives: This study explored the effects of different degradation gradients on bacterial diversity in the rhizospheric soils of herb plants. Methods: The alpha diversity, species composition and correlations of bacterial communities in the rhizospheric soils of herb plants were studied using metagenomics 16SrDNA gene high-throughput sequencing. Results: The diversity of bacterial communities in the rhizospheric soils of herb plants differed during the degradation of desert steppes. An analysis of bacterial community alpha diversity indices showed the bacterial diversity and species evenness of rhizospheric soils were best in moderately degraded desert steppes. Among all samples, a total of 43 phyla, 133 classes, 261 orders, 421 families, 802 genera and 1,129 species were detected. At the phylum level, the predominant bacterial phyla were: Actinobacteria, Proteobacteria, Acidobacteria, Gemmatimonadetes, Chloroflexi, Planctomycetes and Bacteroidetes. At the genus level, the predominant bacterial genera were: RB41, Sphingomonas, WD2101_soil_group_unclassified, Pseudomonas and Actinomyces. The relative abundance of unknown genera was very large, which deserves further research. At the phylum and genus levels, the species abundance levels under slight and moderate degradation were significantly higher than those under extreme degradation. Correlation network diagrams showed there were many nodes in both slightly deteriorated and moderately deteriorated soils, and the node proportions were large and mostly positively correlated. These results indicate the bacterial communities in rhizospheric soils under slight or moderate deterioration are relatively stable. The rhizospheric soil microbes of desert steppes can form a stable network structure, allowing them to adequately respond to environmental conditions. Conclusions: The bacterial communities in the rhizospheric soils of herb plants differ between different degradation gradients. The species number, abundance and diversity of bacterial communities in rhizospheric soils are not directly correlated with degree of degradation. The abundance, species diversity and species abundance of bacterial communities in the rhizospheric soils of moderately degraded desert steppes are the highest and most stable. The soil bacterial diversity is lowest in severely degraded desert steppes.

Cohesin maintains replication timing to suppress DNA damage on cancer genes.

Cohesin loss-of-function mutations are frequently observed in tumors, but the mechanism underlying its role in tumorigenesis is unclear. Here, we found that depletion of RAD21, a core subunit of cohesin, leads to massive genome-wide DNA breaks and 147 translocation hotspot genes, co-mutated with cohesin in multiple cancers. Increased DNA damages are independent of RAD21-loss-induced transcription alteration and loop anchor disruption. However, damage-induced chromosomal translocations coincide with the asymmetrically distributed Okazaki fragments of DNA replication, suggesting that RAD21 depletion causes replication stresses evidenced by the slower replication speed and increased stalled forks. Mechanistically, approximately 30% of the human genome exhibits an earlier replication timing after RAD21 depletion, caused by the early initiation of >900 extra dormant origins. Correspondingly, most translocation hotspot genes lie in timing-altered regions. Therefore, we conclude that cohesin dysfunction causes replication stresses induced by excessive DNA replication initiation, resulting in gross DNA damages that may promote tumorigenesis.

Effects of different soil types on gas exhange parameters and fruits of Hippophae rhamnoides ssp. mongolica "Ulanshalin" plants.

Background: This study aims to explore the growth and production potential of Hippophae rhamnoides ssp. mongolica "Ulanshalin," a pioneer species of soil and water conservation, after being planted in the Yellow River Basin area with serious soil erosion. An analysis of the differences in photosynthesis and fruit yield of H. rhamnoides plants grown in two typical soils in the watershed is key to understanding whether local conditions are suitable for the growth and yield of H. rhamnoides, as well as the impact of the plants on soil and water conservation. Methods: During the growing season, diurnal changes in the gas exchange parameters of Hippophae rhamnoides-like plants growing in Loess soil and Aeolian soil were continuously monitored, and the effects of total nitrogen (TN) and other elements on the net photosynthetic rate (P N) of the plants were analyzed and compared in the two different soil types. The morphological and quality differences of Hippophae rhamnoides fruits were also compared after reaching the ripening stage. Results: (1) There was a significant difference in the composition of Loess soil and of Aeolian soil. The organic matter content and AK content of the Loess soil was significantly higher than in the Aeolian soil, and the pH was closer to neutral. However, the TK content, TP content, and AP content of the Aeolian soil were slightly higher than in the Loess soil, the pH was higher, and it was alkaline. (2) After controlling the light and temperature, with all other external factors consistent, the daily variation trend of P N, T r, and G s in the leaves of H. rhamnoides plants growing in the two different soils were basically the same. There were differences, however, in when these factors reached their peaks. Soil composition had an impact on the photosynthetic characteristics of H. rhamnoides, with TN, TP, AP, and SOM being the main factors promoting the photosynthetic rate of H. rhamnoides P N. The peaks of P N, T r, and G s of H. rhamnoides plants growing in Aeolian soil were higher than those growing in Loess soil. (3) The average stem length of H. rhamnoides plants growing in Aeolian soil was higher than the plants growing in Loess soil. The number of thorns in the branches of plants in the Aeolian soil was relatively low, and the weight of 100 fruits (28.28 g) was significantly higher than the weight of 100 fruits of the H. rhamnoides plants grown in Loess soil (11.14 g). Conclusions: The results of this study show that in the Yellow River Basin area, Aeolian soil is more conducive to the growth of H. rhamnoides plants than Loess soil. H. rhamnoides plants growing in Aeolian soil had good adaptability and stress resistance, and a larger potential for fruit production. These findings provide insights for ecological restoration and the creation of economic value in the Yellow River Basin area.

Effects of stumping on fine root architecture, growth, and physiology of Hippophae rhamnoides.

Background: Fine roots are vital to a plant's ability to absorb water and nutrients. Stumping is a practice that may encourage fine root growth and the rapid recovery of decaying Hippophae rhamnoides plants. However, the effect of stumping on the fine roots and physiological indices is still unknown. The differential indices between stumped forests and non-stumped forests must also be defined. Methods: We recorded the changes in the fine roots of structure H. rhamnoides one year after stumping. Using single factor analysis of variance and general linear models we comprehensively analyzed the number of root tips and the plant's growth and physiological indices in response to stumping. Partial least squares discriminant analysis (PLS-DA) was used to compare fine root growth and physiological indices with and without stumping in order to identify the differential indices. Results: The proportion of root tips in the vertical layers at 30-40 cm and 40-50 cm and in the horizontal layers at 60-80 cm and 80-100 cm, increased after stumping by 1.85%, 2.60%, 1.96% and 4.32%, respectively. In the 0-50 cm soil layer, the fine root dry weight rose by 27.6% compared with the control, which was not significant. However, other indices were significantly different from the control. The proportions in the growth indices in the 30-40 cm and 40-50 cm layers increased after stumping. Stumping had a significant, negative effect on proline and malondialdehyde content, which dropped by 40.95% and 55.32%, respectively, indicating that the harms caused by these two chemicals was alleviated. Stumping had a significant positive effect on root activity and soluble sugar contents, which increased by 68.58% and 36.87%, respectively, and improved the growing ability of fine roots. PLS-DA revealed that malondialdehyde, soluble sugars, root density, and the number of root tips ranked from having the least to greatest effect on the classification of stumping and no-stumping. Conclusions: The process of stumping may promote fine roots growth in H. rhamnoides, and is favorable for their longitudinal development. The fine root growing indices of H. rhamnoides responded positively to this process. Stumping promotes root activity and the creation of soluble sugar to maintain the growth and development of fine roots. It also inhibits the negative effects of proline and malondialdehyde on fine roots. Our study showed that the differential physiological indices were more important for classification than the differential growing indices.

Coordinated variation in root and leaf functional traits of Hippophae rhamnoides treated at different stump heights in feldspathic sandstone areas of Inner Mongolia.

This study was aimed to clarify the effects of stumping on root and leaf traits as well as the tradeoffs and synergies of decaying Hippophae rhamnoides in feldspathic sandstone areas, and to select the optimal stump height that contributed to the recovery and growth of H. rhamnoides. variations and coordination between leaf traits and fine root traits of H. rhamnoides were studied at different stump heights (0, 10, 15, 20 cm, and no stumping) in feldspathic sandstone areas. All functional traits of the leaves and roots, except the leaf C content (LC) and the fine root C content (FRC), were significantly different among different stump heights. The total variation coefficient was the largest in the specific leaf area (SLA), which is therefore the most sensitive trait. Compared to non-stumping, SLA, leaf N content (LN), specific root length (SRL) and fine root N content (FRN) all improved significantly at stump height of 15 cm, but leaf tissue density (LTD), leaf dry matter content (LDMC), leaf carbon to nitrogen ratio (LC : LN), fine root tissue density (FRTD), fine root dry matter content (FRDMC) and fine root carbon to nitrogen ratio (FRC : FRN) all decreased significantly. The leaf traits of H. rhamnoides at different stump heights follow the leaf economic spectrum, and the fine roots show a similar trait syndrome to the leaves. SLA and LN are positively correlated with SRL and FRN and negatively with FRTD and FRC : FRN. LDMC and LC : LN are positively correlated with FRTD and FRC : FRN, and negatively correlated SRL and RN. The stumped H. rhamnoides changes to the 'rapid investment-return type' resource trade-offs strategy, and the growth rate is maximized at the stump height of 15 cm. Our findings are critical to the prevention and control of vegetation recovery and soil erosion in feldspathic sandstone areas.

Relationship between the roots of Hippophae rhamnoides at different stump heights and the root microenvironment in feldspathic sandstone areas.

Background: To solve the withering of Hippophae rhamnoides plantation in the feldspathic sandstone areas of Inner Mongolia and to promote the regeneration, rejuvenation, and sustainability of H. rhamnoides forests. Methods: We stumped aging H. rhamnoides trees at the ground heights of 0, 10, 15, and 20 cm (S1, S2, S3, and S4, respectively) and utilized unstumped trees as the control (CK). We then analyzed the effects of the different stump heights on the roots and the root microenvironment of H. rhamnoides and the relationship between the roots and the root microenvironment in the stumped H. rhamnoides. Results: The root fractal features, root branching rate, root length, root soluble proteins, soil moisture content, and soil nutrients among the different treatments were ranked as S3>S2>S1>S4>CK (P < 0.05). The root topological index, root proline, and malondialdehyde among the different treatments were ranked as S3

Compensatory growth and understory soil stoichiometric features of Hippophae rhamnoides at different stubble heights.

Background: This study was aimed to explore the compensatory growth ability and influence mechanism of Hippophae rhamnoides at the decaying phase in feldspathic sandstone areas of Ordos, and clarify the stubble height when the compensatory growth ability of H. rhamnoides was the strongest. Methods: The H. rhamnoides forests in the decaying phase from an exposed feldspathic sandstone zone of Ordos were chosen. The compensatory growth ability of H. rhamnoides at stubble height of 0 cm (S1), 10 cm (S2), 15 cm (S3), 20 cm (S4) and control (CK) was investigated with H. rhamnoides forests at the decaying stage in the exposed feldspathic sandstone areas of Ordos. Relationships of compensatory growth ability of H. rhamnoides and understory soil properties with understory soil stoichiometric features as well as the response mechanism to stubble height were explored. Results: (1) Overcompensatory growth of H. rhamnoides in feldspathic sandstone areas occurred at all stubble heights. Especially, the plant height compensation index (1.45) and biomass compensation index (1.25) at the stubble height of 15 cm were both larger compared with other stubbling treatments. These results indicate the stubble height of 15 cm can well promote the growth of the ground part of H. rhamnoides. (2) All stubble heights significantly affected the contents and eco-stoichiometric ratios of soil organic carbon (SOC), total nitrogen (TN), total phosphorus (TP) in understory soils, but the influence rules differed. SOC, TN, and TP contents at all stubble heights were larger than those of the control, and maximized at the stubble height of 15 cm. The carbon(C): phosphorus(P) ratio, and nitrogen (N):(P) ratio after stubbling treatments were all lower compared with the control, and minimized to 19.52 and 1.84 respectively at the stubble height of 15 cm. (3) The understory C:N:P stoichiometric ratio of H. rhamnoides in feldspathic sandstone areas is jointly affected by compensatory growth, stubble height, and soil physicochemical properties. The total explanation rate determined from RDA is 93.1%. The understory soil eco-stoichiometric ratio of H. rhamnoides is mainly affected by soil moisture content (contribution of 87.6%) and total porosity (7.9%), indicating soil moisture content is the most influential factor. The findings will offer some new clues for eco-construction and theoretically underlie soil-water loss administration.

Blood-nerve barrier disruption and coagulation system activation induced by mechanical compression injury participate in the peripheral sensitization of trigeminal neuralgia.

Introduction: The aim of this study was to investigate the effect and possible mechanisms of the blood-nerve barrier (BNB) and the coagulation-anticoagulation system in modulating the mechanical allodynia in a trigeminal neuralgia (TN) rat model induced by chronic compression of the trigeminal root entry zone (TREZ). Methods: Von Frey filaments were applied to determine the orofacial mechanical allodynia threshold. The BNB permeability was evaluated by Evans blue extravasation test. Immunohistochemical staining and laser confocal microscopy were used to measure the length of the depletion zones of the nodes of Ranvier in the TREZ, the diameter of nerve fibers and the length of the nodal gap. The transcriptional levels of prothrombin and endogenous thrombin inhibitor protease nexin-1 (PN-1) in the TREZ of TN rats were assessed by RT-qPCR. A Western blotting assay was performed to detect the expression of paranodal proteins neurofascin-155 (NF155) and neurofascin-125 (NF125) in the TREZ. The spatiotemporal expression pattern of thrombin activated receptor (i.e. protease activated receptor 1, PAR1) in TREZ were defined by immunostaining and immunoblotting assays. PAR1 receptor inhibitors SCH79797 were administrated to TN rats to analyze the effect of thrombin-PAR1 on orofacial hyperalgesia. Results: A compression injury of a rat's TREZ successfully induced TN-like behavior and was accompanied by the destruction of the permeability of the BNB and the promotion of prothrombin and thrombin inhibitor protease nexin-1 (PN-1) expression. The expression of the paranodal proteins neurofascin-155 (NF155) and neurofascin-125 (NF125) was increased, while the nodal gap length of the nodes of Ranvier was widened and the length of node-depleted zones was shortened. Moreover, the expression of PAR1 within the TREZ was upregulated at an early stage of TN, and administration of the PAR1 antagonist SCH79797 effectively ameliorated orofacial mechanical allodynia. Conclusion: A compression injury of the TREZ increased the permeability of the BNB and induced disturbances in the local coagulation-anticoagulation system, concomitant with the structural changes in the nodes of Ranvier, thrombin-PAR1 may play a critical role in modulating orofacial mechanical hyperalgesia in a TN rat model.

Extracellular ATP and cAMP signaling promote Piezo2-dependent mechanical allodynia after trigeminal nerve compression injury.

Trigeminal neuralgia (TN) is a type of severe paroxysmal neuropathic pain commonly triggered by mild mechanical stimulation in the orofacial area. Piezo2, a mechanically gated ion channel that mediates tactile allodynia in neuropathic pain, can be potentiated by a cyclic adenosine monophosphate (cAMP)-dependent signaling pathway that involves the exchange protein directly activated by cAMP 1 (Epac1). To study whether Piezo2-mediated mechanotransduction contributes to peripheral sensitization in a rat model of TN after trigeminal nerve compression injury, the expression of Piezo2 and activation of cAMP signal-related molecules in the trigeminal ganglion (TG) were detected. Changes in purinergic P2 receptors in the TG were also studied by RNA-seq. The expression of Piezo2, cAMP, and Epac1 in the TG of the TN animals increased after chronic compression of the trigeminal nerve root (CCT) for 21 days, but Piezo2 knockdown by shRNA in the TG attenuated orofacial mechanical allodynia. Purinergic P2 receptors P2X4, P2X7, P2Y1, and P2Y2 were significantly up-regulated after CCT injury. In vitro, Piezo2 expression in TG neurons was significantly increased by exogenous adenosine 5'-triphosphate (ATP) and Ca2+ ionophore ionomycin. ATP pre-treated TG neurons displayed elevated [Ca2+ ]i and faster increase in responding to blockage of Na+ /Ca2+ exchanger by KB-R7943. Furthermore, mechanical stimulation of cultured TG neurons led to sustained elevation in [Ca2+ ]i in ATP pre-treated TG neurons, which is much less in naïve TG neurons, or is significantly reduced by Piezo2 inhibitor GsMTx4. These results indicated a pivotal role of Piezo2 in peripheral mechanical allodynia in the rat CCT model. Extracellular ATP, Ca2+ influx, and the cAMP-to-Epac1 signaling pathway synergistically contribute to the pathogenesis and the persistence of mechanical allodynia.

Forecast and Analysis on Reducing China's CO2 Emissions from Lime Industrial Process.

China greenhouse gas inventories show that CO2 emissions from the lime industrial process are large scales and closely related to the development of its downstream industries. Therefore, there is high importance to analyze and forecast on reducing China's CO2 emissions from lime industrial process. The aims of this paper are to make up the research gaps in China and provide a quantitative reference for related authorities to formulate relevant policies. The prediction method in this paper is consistent with the published national inventory, which is an activity data based method to predict carbon dioxide emissions from the industrial process of four categories of lime products. Three future scenarios are assumed. The business as usual scenario (BAU) is a frozen scenario. There are two emission reduction scenarios (ERS and SRS) assumed under different emission reduction strength considering combined industrial process CO2 emission reduction approaches from both the production side and the consumption side. The results show that between 2020 and 2050, China's lime industrial process has an increasingly significant CO2 emission reduction potential, enabling both emission intensity reductions and total emission reductions to be achieved simultaneously. Based on the simulation results from emission reduction scenarios, compared with 2012 level, in 2050, the emission intensity can be reduced by 13⁻27%, the total lime production can be reduced by 49⁻78%, and the CO2 emissions in the lime industrial process can be reduced by 57⁻85%.

Single-cell analyses identify distinct and intermediate states of zebrafish pancreatic islet development.

Pancreatic endocrine islets are vital for glucose homeostasis. However, the islet developmental trajectory and its regulatory network are not well understood. To define the features of these specification and differentiation processes, we isolated individual islet cells from TgBAC(neurod1:EGFP) transgenic zebrafish and analyzed islet developmental dynamics across four different embryonic stages using a single-cell RNA-seq strategy. We identified proliferative endocrine progenitors, which could be further categorized by different cell cycle phases with the G1/S subpopulation displaying a distinct differentiation potential. We identified endocrine precursors, a heterogeneous intermediate-state population consisting of lineage-primed alpha, beta and delta cells that were characterized by the expression of lineage-specific transcription factors and relatively low expression of terminally differentiation markers. The terminally differentiated alpha, beta, and delta cells displayed stage-dependent differentiation states, which were related to their functional maturation. Our data unveiled distinct states, events and molecular features during the islet developmental transition, and provided resources to comprehensively understand the lineage hierarchy of islet development at the single-cell level.

[Comparative study on treatment of diabetic gastroparesis by acupuncture and Western medicine].

OBJECTIVE: To compare therapeutic effects of acupuncture and mosapride in relieving diabetic gastroparesis. METHODS: Forty cases were randomly divided into a treatment group and a control group, 20 cases in each group. The treatment group were treated by acupuncture at Zhongwan (CV 12) and Zusanli (ST 36), and the control group by oral administration of mosapride 5 mg, t. i. d. Their therapeutic effects were evaluated by indexes of therapeutic effect. RESULTS: The total effective rate was 95.0% in the treatment group and 83.3% in the control group with a significant difference between the two groups (P<0.05), and the adverse effect in the treatment group was less than that in the control group (P<0.05). CONCLUSION: Acupuncture can significantly relieve diabetic gastroparesis, the therapeutic effect being better than mosapride, with a less adverse effects.